Potassium Carbonate → tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate

HRID 634156ノート

反応式

HRID 634156 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([C:13]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:20]=4)[N:15]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:14]=3)[CH:10]=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Br[C:39]1[S:40][C:41]([S:44][CH3:45])=[N:42][N:43]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:45][S:44][C:41]1[S:40][C:39]([C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][CH:18]=2)[N:15]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:14]=[C:13]3[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[N:12]=2)=[N:43][N:42]=1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 222696212-Bromo-5-(methylsulfanyl)-1,3,4-thiadiazoleHCID 68328848tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

生成物 1

HCID 68327982tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate収率 47.1%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6344Dichloromethane溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
100 °C

実験手順

A glass microwave reaction vessel was charged with tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (1.20 g, 2.374 mmol) and 2-bromo-5-(methylthio)-1,3,4-thiadiazole (1.002 g, 4.75 mmol) in p-dioxane/H2O (4:1, 15 mL) followed by potassium carbonate (0.984 g, 7.12 mmol, Aldrich) and Pd(PPh3)4 (0.137 g, 0.119 mmol, Strem). The reaction was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 2 h. The mixture was diluted with DCM (150 mL) and washed with H2O. The organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-18% EtOAc in DCM) to give tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate (570 mg, 1.118 mmol, 47.1%) as a yellow solid. MS (ESI, pos. ion) m/z: 510 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 8.91 (1H, s), 8.17-8.32 (2H, m), 7.98 (1H, dd, J=8.7, 1.7 Hz), 7.65 (1H, t, J=8.0 Hz), 7.18 (1H, d, J=7.4 Hz), 6.70 (1H, d, J=8.4 Hz), 3.92-4.01 (4H, m), 3.68-3.77 (4H, m), 2.84 (3H, s), 1.72 (9H, s).

後処理

  1. customA glass microwave reaction vessel
  2. washwashed with H2O
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 0-18% EtOAc in DCM)

出典と根拠

ORDレコード
ord-72731119dab5465da98cdbfbe1a87e2d
出典データセット
uspto-grants-2016_04
特許番号
US09321756B2

反応ノート

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